MiR-338-3p improved lung adenocarcinoma by AKAP12 suppression

Introduction: This study aimed to explore the biological functions of AKAP12 in lung adenocarcinoma and investigate the interaction between AKAP12 and miR-338-3p.

Material and methods: Sixty-one differentially expressed genes in lung adenocarcinoma and adjacent normal tissues were first analyzed by TCGA. Immunohistochemistry and quantitative reverse transcription PCR (qRT-PCR) were further utilized to confirm aberrant AKAP12 expression in tumor tissues. The influences of AKAP12 on proliferation, invasion and migration, and apoptosis of lung adenocarcinoma were investigated by clone formation assay and MTT assay, transwell assay, and flow cytometry analysis respectively. TargetScan and miRanda databases predicted the binding sites of miRNAs on AKAP12 3'-UTR and structure changes were validated by RNA folding form. The target relationship between miR-338-3p and AKAP12 was confirmed by the dual-luciferase reporter system. Disease-free survival (DFS) and overall survival (OS) curves were generated with Kaplan-Meier plotter according to the TCGA data and the correlation among AKAP12 expression, miR-338-3p expression and prognosis was also analyzed.

Results: AKAP12 was upregulated in lung adenocarcinoma tissues and cells (all p < 0.01), and negatively correlated with prognosis outcomes of patients (both p < 0.05). High expression of AKAP12 promoted proliferation, invasion and migration of cancer cells, and inhibited cell apoptosis (all p < 0.05). MiR-338-3p could directly bind to the 3'-UTR of AKAP12 and showed most significant suppression on AKAP12 expression among four predicted miRNAs (all p < 0.01). Additionally, miR-338-3p could suppress AKAP12 in lung adenocarcinoma, improving prognosis (all p < 0.05).

Conclusions: AKAP12 acts as a tumor promoter in lung adenocarcinoma development. Upregulation of MiR-338-3p could suppress AKAP12 expression in lung cancer cells and contribute to a better prognosis.